Compatibility of Radix Stephaniae Tetrandrae and Ramulus Cinnamomi: Radix Stephaniae Tetrandrae has bitter taste, cold, diuresis, clearing away heat and expelling wind, dredging collaterals and relieving pain, and damp-heat in lower energizer; Ramulus Cinnamomi can dry and warm collaterals, remove arthralgia and relieve pain, and warm yang to turn qi into water. The combination of the two can enhance the efficacy of expelling wind and removing dampness, removing arthralgia and relieving pain. Treating severe swelling and pain of lower limbs caused by wind-cold-dampness arthralgia and joint pain caused by meridian invasion with the efficacy of warming yang, transforming qi and inducing diuresis to reduce swelling.
Compatibility of Radix Stephaniae Tetrandrae and Radix Astragali: Radix Stephaniae Tetrandrae has bitter taste, cold, diarrhea, diuresis, detumescence, expelling wind and removing dampness; Astragalus warms and tonifies middle energizer, tonifies qi and consolidates exterior, and promotes diuresis and detumescence. Astragalus tends to tonify the body and promote ascension. Both of them have the functions of benefiting qi, inducing diuresis and reducing swelling. It can be used for the treatment of edema due to geomantic omen, sweating with evil breath, depression, dysuria, wet swelling and numbness of limbs.
1. Analgesic and Anti-inflammatory Effects of Tetrandrine; Tetrandrine A, Tetrandrine B and Tetrandrine C all have analgesic effects. Total alkaloids have the strongest effect, the effective dose is 50mg/kg, and the lethal dose is 24 1 ~ 25 1mg/kg. The analgesic effect of tetrandrine is better than that of tetrandrine A and tetrandrine B, so it has no practical value. The liquid extracts or decoctions of tetrandrine and tetrandrine have analgesic effects, and the effect of tetrandrine is stronger than that of tetrandrine. The antihistamine diphenhydramine can significantly enhance the analgesic effects of tetrandrine and tetrandrine without affecting their toxicity. It has also been reported that when the dosage of tetrandrine exceeds a certain dose, its analgesic effect is weakened or disappeared, which may be because the larger dose of tetrandrine can excite the central nervous system, thus weakening the analgesic effect.
It has been reported that tetrandrine has central inhibitory effects such as sedation, analgesia and cooling. It can inhibit the spontaneous activity of mice, enhance the central inhibition of pentobarbital sodium and chloral hydrate, antagonize the excitement of caffeine and amphetamine, delay the latent period of convulsion caused by pentylenetetrazol and strychnine, and prolong the death time of mice after convulsion.
Tetrandrine A and B have certain anti-inflammatory effects on formalin-induced arthritis in rats. The effect of tetrandrine A is stronger than that of tetrandrine B, and its effect is similar to that of cortisone, stronger than that of sodium salicylate and weaker than that of phenylbutazone. The effect disappears after adrenalectomy, suggesting that tetrandrine A can directly act on adrenal gland, stimulate pituitary-adrenal system, enhance adrenal cortex function, and stimulate adrenal cortex in a non-specific way. Tetrandrine also has anti-inflammatory effect on experimental ear shell burn in rabbits. It can reduce the vascular permeability of skin trypan blue experimental rats. Tetrandrine hydrochloride can obviously inhibit paw swelling, cotton granuloma proliferation, abdominal capillary permeability and ear shell swelling induced by egg white, formaldehyde and carrageenan in rats. This effect still exists after bilateral adrenalectomy in rats. Tetrandrine can not prolong the survival time of young rats after adrenalectomy, but it can significantly reduce the amount of PGE released by inflammatory tissues, increase the plasma cortisol concentration, obviously shrink the thymus gland and increase the weight of adrenal gland.
Both tetrandrine and anisodamine have inhibitory effects on arthritis induced by other drugs in experimental animals, which are equivalent to those of phenylbutazone, but tetrandrine has slightly stronger anti-inflammatory effect than anisodamine.
4. Anti-allergic effect Tetrandrine has a wide range of anti-allergic effects, which is both an antagonist and a blocker of allergic mediators. It can obviously reduce the incidence of severe shock symptoms in rabbits with anaphylactic shock caused by whole egg white, but has no obvious effect on mortality. Tetrandrine has no effect on histamine shock in guinea pigs. Tetrandrine can inhibit passive skin allergic reaction in rats and allergic contraction of isolated ileum in sensitized guinea pigs. Inhibition of histamine and acetylcholine-induced asthma in guinea pigs and contraction of isolated ileum in guinea pigs; Tetrandrine itself has no effect on the contraction and relaxation of tracheal smooth muscle, but it can obviously antagonize the contraction of tracheal smooth muscle caused by slow reaction substance SRS-A during allergic reaction. Tetrandrine aerosol inhalation, intraperitoneal injection, oral administration or pre-administration can protect guinea pigs from SRS-A wheezing, indicating that the incubation period of wheezing is obviously prolonged and the number of convulsions caused by wheezing is reduced.
Tetrandrine is a calcium antagonist with a wide range of actions, which may be the mechanism of its antiallergic effect.
3. Influence on cardiovascular system.
A. Effect on the heart: Animal experiments show that a small dose of tetrandrine can enhance the contractility and increase the amplitude of the heart, while a large dose can inhibit the heart to varying degrees. Intravenous injection of tetrandrine 10mg/kg in anesthetized dogs can inhibit myocardial contractility and pump function, significantly slow down the heart rhythm, reduce the total resistance of peripheral blood vessels and stress time index, suggesting that myocardial energy consumption is reduced, but these effects can be antagonized by calcium chloride.
Tetrandrine has certain protective effect on experimental myocardial infarction. After taking the medicine, the blood pressure decreased slightly and the heart rate slowed down slightly, which was beneficial to myocardial ischemia. Tetrandrine has obvious preventive effect on acute hypoxic-ischemic myocardial injury caused by pituitrin, but its protective effect on acute myocardial necrosis caused by isoproterenol is not obvious enough. However, it has also been reported that tetrandrine has protective effect on isoproterenol-induced hypoxia and necrotizing electrocardiogram in rats.
In vitro and whole animal experiments show that tetrandrine can antagonize arrhythmia caused by cardiac glycoside, aconitine, calcium ion and chloroform plus adrenaline, but it can't increase the threshold of fibrillation. Increasing the dosage of ouabain to produce positive inotropic effect, the maximum peak value of action remains unchanged, and the therapeutic width does not increase. The antiarrhythmic mechanism of tetrandrine is to inhibit calcium influx. -It has nothing to do with receptors, but is related to ion transport affecting myocardial cell membrane.
B. Effect on coronary artery flow: Tetrandrine has obvious dilating effect on coronary vessels. The increase of flow rate is related to the drug concentration in isolated rabbit coronary vessels. When the concentration is high, the effect occurs quickly and lasts for a short time. When the concentration is low, it will happen slowly and last for a long time. It can also significantly increase the coronary flow during cardiac arrest. In vitro and overall experiments show that tetrandrine can reduce myocardial oxygen consumption and oxygen uptake, and its coronary artery dilating effect has nothing to do with adrenaline and catecholamine. Myocardial contractility, heart rate and blood pressure have little effect on coronary flow. They act directly on coronary vessels to increase coronary flow. Tetrandrine can antagonize the coronary artery contracture caused by ouabain, but its effect can be antagonized by high Ca++. It has also been reported that tetrandrine mainly inhibits the potential-dependent Ca++ channel on the cell membrane and prevents Ca++ from entering the cell through this channel, but has no effect on the receptor-activated Ca++ channel. Tetrandrine has no effect on receptor-activated calcium channels. -Receptor blockers, because they do not block the relaxation of isoproterenol on the coronary artery system.
C. Effect on blood pressure: Many alkaloids of tetrandrine have the effect of lowering blood pressure in many animals. Tetrandrine and B can obviously reduce the blood pressure of anesthetized cats by intravenous injection, intramuscular injection or intragastric administration, and the role of A is particularly significant. 3 ~ 6 mg/kg can reduce blood pressure by 50% ~ 65% for more than 65,438+0 hours, and cardiac contractility is only temporarily weakened during hypotension. There was no significant change in heart rate and conduction. Intravenous injection can also reduce blood pressure in anesthetized dogs. The hypotensive principle of tetrandrine is to directly dilate blood vessels, simulate M-like action, and inhibit vascular motor center and sympathetic nerve center. It can effectively reduce the plasma concentration of arterial blood vessels, selectively dilate arterial resistance vessels, reduce afterload and increase cardiac output. Tetrandrine can lower blood pressure without obvious reflex heart rate increase. This is different from vasodilator hydralazine and so on. B also has antihypertensive effect, which is the same as that of A, but its effect is weaker than that of A, and it is easy to produce rapid tolerance. The hypotensive effect of C is stronger than that of A, which has nothing to do with vagus nerve and the heart is not inhibited.
4. Effect on smooth muscle Tetrandrine can inhibit isolated rabbit small intestine and uterine smooth muscle of guinea pig or rabbit, but its effect is dose-dependent. Low concentration of tetrandrine can increase the tension and enhance the rhythmic contraction of isolated rabbit small intestine, while high concentration can reduce the tension and rhythmic contraction. It has no obvious effect on the uterus in vitro and in situ. Higher dose can partially inhibit the spasmodic contraction caused by pilocarpine and barium chloride, and cause the contraction of bronchial smooth muscle in guinea pigs and cats. This is caused by the release of histamine. Tetrandrine can obviously inhibit or relax the uterine contraction induced by oxytocin and Ca++ after high K+ depolarization, and its mechanism is that Ca++ inhibits uterine smooth muscle. The relaxation effect of tetrandrine on vascular smooth muscle was not blocked by phentolamine. -Receptor or propranolol blockade? Receptor. The experiment also proved that tetrandrine relaxes vascular smooth muscle by selectively blocking slow channel Ca++ influx, because its inhibitory strength on smooth muscle contraction caused by potassium chloride, calcium chloride and norepinephrine is similar to that of calcium channel blocker Umaian. Tetrandrine can increase the tension and enhance the rhythmic contraction of isolated rabbit intestine at low concentration, and reduce the tension and weaken the rhythmic contraction at high concentration.
⒌ effect on striated muscle: Various alkaloids of tetrandrine can relax striated muscle. It is reported that the total alkaloids of tetrandrine and its methylated compounds have the function of relaxing striated muscles, and can be used as auxiliary drugs for anesthesia of traditional Chinese medicine. An alkaloid (not a, b, c) proposed in tetrandrine has obvious effect of relaxing striated muscles and can be antagonized by neostigmine.
Anti-cancer effect Tetrandrine has obvious anti-cancer effect. It can kill Ehrlich ascites cancer cells in vitro and slightly inhibit the growth of S 180 cells. It has obvious cytotoxic effect on KB cells and Hela cells, and has certain inhibitory effect on liver cancer cells. With the increase of tetrandrine concentration, the damage degree of liver cancer cells is more serious, but the low concentration (3.2? Tetrandrine (g/ml) has slight damage to liver cancer cells, and the damaged cells tend to recover with the extension of culture time. The drug concentration is 16 ~ 24? At g/ml, it has obvious damage to human hepatocellular carcinoma cell line, and the drug concentration is 80? G/ml, which is lethal to cells. In vivo, W256 has obvious inhibitory effect on ascites, B-type and T-type Ehrlich ascites carcinoma and mouse hepatocellular carcinoma. Experiments show that its anti-cancer effect is related to antibacterial and anti-inflammatory, and has nothing to do with the central and peripheral nervous system.
The antibacterial effects of tetrandrine A and tetrandrine B have anti-amoeba effects in vitro, and the effects are stronger than berberine. Tetrandrine has an effect on Shigella at the concentrations of 1:200 and 1:400, but has no effect on Shigella sonnei and Shigella flexneri. Tetrandrine also has antifungal effect in vitro.